Hyper IgM Syndrome Type 1 (HIGM-1) is the

X-linked Sex linked describes the sex-specific patterns of inheritance and presentation when a gene mutation (allele) is present on a sex chromosome (allosome) rather than a non-sex chromosome (autosome). In humans, these are termed X-linked recessive, ...

variant of the

hyper IgM syndrome Hyper IgM syndrome describes a group of primary immune deficiency disorders characterized by defective CD40 signaling; ''via'' B cells affecting class switch recombination (CSR) and somatic hypermutation. Immunoglobulin (Ig) class switch reco ...

. The affected individuals are virtually always male, because males only have one

X chromosome The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex ...

, received from their mothers. Their mothers are not symptomatic, even though they are carriers of the allele, because the trait is recessive. Male offspring of these women have a 50% chance of inheriting their mother's mutant allele.

Signs and symptoms

A patient presenting with hyper IgM syndrome may be affected by simple infectious organisms in exposed regions like the respiratory system. Vaccination against pathogenic organisms may not help these individuals, because vaccinating them does not properly stimulate production of antibodies. Symptoms can include: * Fever (recurrent infections) * Low counts of IgA, IgG and IgE antibodies * CD40L not reactive in T cells * Recurrent sinopulmonary and GI infections with pyogenic bacteria and opportunistic organisms, and cutaneous manifestations including pyodermas extensive warts.

Pathogenesis

This variant of the hyper IgM syndrome is caused by mutation of the CD40LG gene. The genetic locus for this gene is Xq26. This gene codes for the

CD40 Cluster of differentiation 40, CD40 is a costimulatory protein found on antigen-presenting cells and is required for their activation. The binding of CD154 ( CD40L) on TH cells to CD40 activates antigen presenting cells and induces a variety of d ...

ligand In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elec ...

, which is expressed on T cells. When the CD40 ligand binds CD40 on B cells, then the B cell switches from producing IgM to producing IgA or

IgG Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...

. In these patients a biopsy of a lymph node may show poor development of structural and germinal centers because of the lack of activation of B cells by the T cells in them.

Diagnosis

Treatment

Patients presenting with this disease undergo antibiotic treatment and gammaglobulin transfusions. Antibiotics are used to fight off the pathogenic organisms and the gammaglobulin helps provide a normal balance of antibodies to fight the infection. Bone marrow transplantation may be an option in some cases. OMIM
308230

References

External links

{{X-linked disorders Immune system disorders Rare syndromes